Tuberculosis (TB) is a major global public health problem, closely linked to the HIV epidemic. The detection of Mycobacterium tuberculosis (MTb) infection in high risk populations, and the delivery of preventive therapy are critical components of TB control efforts. HIV infection is the most potent risk factor for progression of MTb infection to clinical TB. Drug users (DUs) have a high prevalence of MTb and HIV infection and thus represent an important group to target for TB screening. However, the factors, settings and behaviors which contribute to the high prevalence are poorly characterized, and adherence to TB screening and preventive therapy are problematic. Identifying factors associated with a greater prevalence of TB infection among DUs may be valuable in guiding the development of effective TB services and in targeting interventions to disrupt transmission. We have documented a high prevalence of TB infection among active New York City (NYC) DUs, and a marked rise in this prevalence with age and years of drug use, suggesting a high average annual incidence of TB infection. Nonetheless, we have demonstrated that with appropriate program models, high rates of acceptance and adherence to voluntary TB screening and preventive therapy can be achieved. We now propose to: 1) estimate the annual risk of TB infection among NYC DUs from tuberculin skin test prevalence data; 2) to characterize the prevalence of TB infection, and factors associated with TB infection, among specific groups of DUs; and to examine the factors associated with TB infection among non-injection DUs; 3) to determine the effectiveness of a monetary incentive at improving the adherence of tuberculin positive DUs to referral from a syringe exchange program for screening chest radiographs; 4) to evaluate TB DOPT for DUs with respect to acceptance, retention, and adherence in two DOPT program models; and for DOPT at the syringe exchange, to examine DOPT retention and adherence with respect to retention in syringe exchange; 5) to pilot the feasibility of conducting serial TB skin testing for IDUs at a syringe exchange (as a model for conduction longitudinal health care interventions at a syringe exchange); and to examine adherence to serial TB screening with respect to retention in syringe exchange; and 5a) to directly measure the incidence of new TB infection among IDUs at a syringe exchange program.